Project Summary/Abstract The hippocampus is one of a select few brain regions that retain the ability to generate neurons in adulthood. Research in human patients and animal models suggests that increases and decreases in neurogenesis alter memory function and contribute to the etiology and treatment of emotional disorders. Despite almost 15 years of research linking adult neurogenesis to memory and emotional regulation, almost nothing is known about the circuit and coding mechanisms through which adult neurogenesis influences these processes. The recent development (with BRAIN Initiative support) of head-mounted minimicroscopes provides an unprecedented opportunity to image activity of adult-born neurons as animals learn and behave. Under this award, we will acquire equipment and training that will enable our lab to sustainably incorporate miniscope imaging into our research program on adult neurogenesis. In addition, we will perform calcium imaging experiments in freely moving mice as they explore contexts and undergo contextual fear conditioning, a model learning paradigm that is sensitive to perturbations of adult neurogenesis. Using optogenetic silencing of adult-born neurons, we will characterize how adult-born neurons influence coding of context memory in dentate gyrus, a region required for context memory. These experiments will provide new and previously unattainable insights into the mechanisms through which adult-born neurons regulate hippocampal memory, and they will enable our lab to integrate miniscope technology in a sustainable way in multiple ongoing research streams.

Project Narrative/Public Health Relevance Statement Despite the vast amount of correlational and experimental data identifying adult neurogenesis—the generation of nerve cells in the adult hippocampus— as a clinically important form of brain plasticity, very little is known about the precise circuit mechanisms through which adult-born neurons influence memory, emotion and related aspects of brain heath. This award will help address this gap in our understanding by supporting a neurogenesis research lab in acquiring new techniques for imaging the activity of adult-born neurons in behaving mice. The proposed research and training will further our understanding of the mechanisms through which natural and disease-related changes in adult neurogenesis influence mood and cognition.